About our Project

Epithelial ovarian cancer (EOC) is the most lethal gyncaecologica malignancy. The predominance of aggressive Type II tumours (comprised of high-grade serous, high-grade endometrioid, and undifferentiated carcinomas) that are characterised by nearly ubiquitous p53 mutations (> 96% of patients) and primary or acquired resistance to platinum-based chemotherapy is the reason for the high mortality rate.

There is a pressing need for more effective, innovative treatment strategies to particularly improve survival in this major subgroup of EOC patients. The GANNET53 project aims to achieve this goal by applying a highly innovative treatment concept whose scientific rationale directly grew out from solid basic research findings by members of the GANNET53 consortium.

Two CLINICAL TRIALS, i.e. the GANNET53 trial and the EUDARIO trial will apply a DRUG STRATEGY inhibiting the central chaperone Hsp90 (heat shock protein 90) in p53 mutant (mutp53) EOC.

In addition, extensive TRANSLATIONAL RESEARCH is done by some of Europe's leading researchers:

  • Biobank: collection, deposition and delivery of biomaterialseCRFs, biobank database, Central Histopathological Review (CHR);
  • Companion diagnostics: exact determination of p53 status, molecular efficacy testing, functional molecular test (proximity ligation assay), CTC analysis;
  • Mouse models and human xenografs: stringent in vivo Genetic and Pharmacologic Proof-of-Principle for the underlying treatment concept in engineered mutp53 knock-in mice, stringent tests of the Ganetespib-mediated preferential killing of mutp53 cancer cells in human ovarian cancer models;

The GANNET53 Project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602602.

Here you find more information about the CLINICAL TRIALS and TRANSLATIONAL RESEARCH.

Who We Are

We established a highly efficient scientific consortium with a strong track record of proven capability and manpower to perform this multicentre clinical trial and assess our innovative therapeutic concept in this deadly disease. Our consortium consists of nation-wide clinical trial groups in gynaecological oncology and high-volume university centres as well as noted p53 scientists and 3 innovative SMEs. Since ovarian cancer is defined as a rare cancer, a scale at the European level is crucial for the planned clinical trial.

Here you find more information about the GANNET53 Project Partners.

Scientific Background

 Alterations in the p53 tumour suppressor gene, often called the Guardian of the Genome (citing Sir David Lane, co-discoverer of p53 in 1979, and member of our External Advisory Board) are the most common genetic alterations in human cancers. p53 mutations occur in >50% of all human cancers. In sharp contrast to all other tumor suppressor genes, which typically lose protein expression upon mutation, 85% of p53 mutations are missense mutations in the DNA-binding domain, and they frequently generate conformationally aberrant proteins (full-length ‘mutp53’). For the longest time, mutant p53 (mutp53) protein was considered a 'dead' protein that has lost its potent tumor suppressor function (Brown et al, Nat Rev Cancer 9:862-73, 2009; Vaseva and Moll, Biochem Biophys Acta 1787:414-20, 2009), and was just lying around as waste in the tumor cell. Recently however, new insights changed this concept and established that mutp53 acquires broad new oncogenic activity (gain-of function, GOF).

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Recent data from the EUROCARE database showed an age-standardised 5-year overall survival rate of EOC patients of only 36.1% (95% CI 35.4–36.8; Oberaigner et al, Acta Oncol 51:441-53, 2012). In Europe, 66,700 women are diagnosed with ovarian cancer and 41,900 die of the disease every year. This high mortality rate is due to the predominance of late-stage diagnoses, a high relapse rate after primary therapy and poor response of metastatic platinum-resistant tumours to salvage regimens. 70% of EOC patients present with metastasised disease at time of primary diagnosis (peritoneal carcinosis).

The current standard of primary therapy is cytoreductive surgery and adjuvant chemotherapy with Carboplatin and Paclitaxel. Initial response rates are high, but inevitably the vast majority of patients will relapse in short time and ultimately die of the disease.

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The test drug Ganetespib

The GANNET53 trial and the EUDARIO trial applies the safest, most effective and clinically most advanced Hsp90 (heat shock protein 90) inhibitor available.

Ganetespib is a highly potent, 2nd generation Hsp90 inhibitor (synthetic small molecule) developed by Aldeyra Therapeutics (Lexington, MA, USA). Aldeyra agreed to provide the drug for this entire trial at no charge.

Ganetespib has been studied in 5 completed Synta-sponsored clinical trials (studies 9090-02, 9090-03, 9090-04, 9090-05, and 9090-07) and 3 completed Synta-sponsored studies in normal healthy volunteers (9090-12, 9090-13, and 9090-15). Ganetespib is being studied in 6 ongoing Synta-sponsored clinical trials. Studies include: one phase I study, three phase II studies, one phase IIb study, and one phase III study. Ganetespib is also being studied in 17 investigator-sponsored clinical trials (ISTs), 8 of which are currently enrolling patients. The majority of ISTs are proof-of-concept studies across a variety of tumour types as well as haematologic malignancies. The ISTs currently enrolling include: two phase I/II studies, two phase I studies, and four phase II studies. Please refer to http://clinicaltrials.gov for further information.